Delicate balance between functionally required flexibility and aggregation risk in a β-rich protein.

ABSTRACT: Susceptibility to aggregation is general to proteins because of the potential for intermolecular interactions between hydrophobic stretches in their amino acid sequences. Protein aggregation has been implicated in several catastrophic diseases, yet we still lack in-depth understanding about how proteins are channeled to this state. Using a predominantly β-sheet protein whose folding has been explored in detail, cellular retinoic acid-binding protein 1 (CRABP1), as a model, we have tackled the challenge of understanding the links between a protein's natural tendency to fold, 'breathe', and function with its propensity to misfold and aggregate. We identified near-native dynamic species that lead to aggregation and found that inherent structural fluctuations in the native protein, resulting i

SUBMITTER: Ferrolino MC 

PROVIDER: S-EPMC3946317 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature